Medicine and Health Sciences Commons^™

Understanding Cancer Patients' Desire To Quit Tobacco Without Assistance: A Mixed-Methods, Longitudinal Study, Tia Borger

Theses and Dissertations--Psychology

Introduction: Unassisted attempts to quit tobacco are a well-established reason for quit failure. Nonetheless, many cancer patients prefer to make a quit attempt without using evidence-based tobacco treatment. This study aimed to understand the rationale that underlies cancer patients’ desire to quit tobacco without assistance and to track longitudinally the smoking cessation outcomes of patients with this preference. Method: In a mixed-methods, longitudinal study, 35 cancer patients who were current tobacco users and declined tobacco treatment because of the desire to quit on their own provided data via three questionnaires and 1-2 semi-structured interviews across 60 days. Participants were recruited …

Investigation Of Folate-Poly(Glutamic Acid)/Polyethylenimine/Dna Complexes For In Vitro Gene Delivery, Caleb Akers

Theses and Dissertations--Pharmacy

Gene therapy is currently being studied as a treatment for a variety of indications, including cancer, infectious disease, and cardiovascular diseases, among others. While many of the early treatments in the field involved the use of viral delivery methods, various safety, ethical, and financial concerns limit the potential uses of this methodology. As such, more recent research has focused on developing non-viral delivery platforms to alleviate some of the issues inherent in viral delivery. Recently, the release of the COVID-19 vaccines from Pfizer and Moderna represents a promising use of non-viral delivery as both utilized a lipid-based delivery vector.

Despite …

Design, Synthesis, And Anticancer Properties Of Ru(Ii) Complexes With Organometallic, “Expanded” Bipyridine, And O,O’-Chelating Ligands, Raphael Ryan

Theses and Dissertations--Chemistry

Cancer is a worldwide public health crisis that requires new and improved drugs to be developed to extend survival rates and improve quality of life for the patient. Platinum-based drugs are used in approximately 50% of cancer treatment regimens. These drugs are highly effective in many kinds of cancer; however, cancers can develop platinum resistance and these drugs have troubling side effects that reduced their use and efficacy. To overcome these disadvantages, many other metals have been studied for their anticancer properties. Notably, the anticancer properties of ruthenium-based agents have drawn considerable attention with multiple ruthenium complexes entering clinical trials. …

Colorectal Cancer Differences In Staging And Survival: Appalachian And Non-Appalchian Kentuckians, Ripley Lucas

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Colorectal cancer is the third most commonly diagnosed cancer in the United States. Historically, the Appalachian region of Kentucky has experienced disparities in colorectal cancer screening and survival as compared to both the non-Appalachian region of the state and the United States. The aim of this paper is to investigate the differences in cancer staging and survival after diagnosis in Appalachian and non-Appalachian Kentuckians. The present time period of study is a retrospective, population-based cohort with data taken from the Kentucky Cancer Registry. Binomial logistic regression and Cox proportional hazards models were used to estimate unadjusted and adjusted odds ratios …

Evaluating Colorectal Cancer Screening Rates In An Urban Primary Care Practice, Kristen Makowski

DNP Projects

Colorectal cancer accounts for 8% of all cancer deaths and can be prevented through timely removal of colon polyps. Despite recommendations for routine screening, approximately 31.2% of patients go unscreened for this disease (Centers for Disease Control and Prevention, 2018). The purpose of this project was to determine screening rates and documentation mechanisms for colorectal cancer in an urban primary care practice, to determine how many patients completed the screening, and to present findings to the practice providers along with exploring ways to increase screenings. An additional purpose of this project was to determine and identify patient demographics which can …

The Stimulation Of Dendritic Cells By Cationic Lipids, John Peyton Bush

Theses and Dissertations--Medical Sciences

The discovery that cationic lipids can independently stimulate the immune system has generated interest in their potential as vaccine adjuvants. Here, we show that the cationic lipid R-DOTAP can independently stimulate type 1 interferon production in dendritic cells in both primary culture and immortalized cell culture. Levels of type 1 interferon production are cell line-dependent and limited in vitro by lipid-induced cell death. We show that cationic lipids can independently activate TLR-7 and TLR-9, suggesting a mechanism for type 1 interferon induction. This TLR-stimulatory activity is not restricted to R-DOTAP and can be extended to other similar cationic lipids in …

Semisynthetic Aurones: A Family Of Newly Discovered Tubulin Inhibitors As Antineoplastic Agents, Yanqi Xie

Theses and Dissertations--Molecular and Cellular Biochemistry

Aurones belong to an uncommon class of plant flavonoids that provide the bright yellow coloration of some ornamental flowers and that possess a range of biological activities. Structure-activity relationships (SAR) in the aurone pharmacophore identified heterocyclic variants of the (Z)-2-benzylidene-6-hydroxybenzofuran-3(2H)-one scaffold that possessed low nanomolar in vitro potency in cell proliferation assays using various cancer cell lines, in vivo potency in prostate cancer PC-3 xenograft and zebrafish models, selectivity for the colchicine-binding site on tubulin, and absence of appreciable toxicity. Among the biologically active analogs developed in the course of this dissertation work were (Z …

Towards The Rational Design And Application Of Polymers For Gene Therapy: Internalization And Intracellular Fate, Landon Alexander Mott

Theses and Dissertations--Chemical and Materials Engineering

Gene therapy is an approach for the treatment of acquired cancers, infectious disease, degenerative disease, and inherited genetic indications. Developments in the fields of immunotherapies and CRISPR/Cas9 genome editing are revitalizing the efforts to move gene therapy to the forefront of modern medicine. However, slow progress and poor clinical outcomes have plagued the field due to regulatory and safety concerns associated with the flagship delivery vector, the recombinant virus. Immunogenicity and poor transduction in certain cell types severely limits the utility of viruses as a delivery agent of nucleic acids. As a result, significant efforts are being made to develop …

The Development Of Novel Proteasome Inhibitors For The Treatment Of Multiple Myeloma And Alzheimer’S Disease, Min Jae Lee

Theses and Dissertations--Pharmacy

Over a decade, proteasome inhibitors (PIs), bortezomib, carfilzomib (Cfz) and ixazomib, have contributed to a significant improvement in the overall survival for multiple myeloma (MM) patients. However, the response rate of PI was fairly low, leaving a huge gap in MM patient care. Given this, mechanistic understanding of PI resistance is crucial towards developing new therapeutic strategies for refractory/relapsed MM patients.

In this dissertation work, we found H727 human bronchial carcinoid cells are inherently resistant to Cfz, yet susceptible to other PIs and inhibitors targeting upstream components of the ubiquitin-proteasome system (UPS). It indicated H727 cells may serve as a …

Evaluating The Effect Of A Nurse Navigator In Increasing Colorectal Screening, Christine Njogu

DNP Projects

PURPOSE: The purpose of this study is to evaluate the effectiveness of a nurse navigator in increasing colorectal (CRC) screening in primary care setting.

METHODS: This was a descriptive retrospective study of the effect of nurse navigators in increasing colorectal screening in primary care settings within Jefferson county and its surrounding counties. The sample consisted of 200 patient chart reviews for the period of September 1st through December 31st, 2017. Rates of colorectal screening were compared in those who received a nurse navigator call and those who did not.

RESULTS: Overall screening rates were 44.6%. A distinct increase in screening …

Exploring The Effect Of Chronic Inflammation On Response To Immune Checkpoint Inhibitors In Cancer, Sherif M. El-Refai

Theses and Dissertations--Pharmacy

Precision medicine has allowed for the development of monoclonal antibodies that unmask the anti-tumor immune response. These agents have provided some patients durable clinical benefit. However, PD-1 and PD-L1 inhibitor therapies are effective in a small group (10-20%) of non-small cell lung cancer (NSCLC) patients when used as single-agent therapy. The approved companion diagnostic is expression of the immune cell surface molecule, programmed death ligand 1 (PD-L1), on tumors measured by immunohistochemistry (IHC). Studies in tumor biology and immune surveillance dictate that PD-1 inhibitor efficacy should depend on the level of PD-L1 expression; however, the literature has not followed with …

The Development Of Novel Non-Peptide Proteasome Inhibitors For The Treatment Of Solid Tumors, Zachary C. Miller

Theses and Dissertations--Pharmacy

The proteasome is a large protein complex which is responsible for the majority of protein degradation in eukaryotes. Following FDA approval of the first proteasome inhibitor bortezomib for the treatment of multiple myeloma (MM) in 2003, there has been an increasing awareness of the significant therapeutic potential of proteasome inhibitors in the treatment of cancer. As of 2017, three proteasome inhibitors are approved for the treatment of MM but in clinical trials with patients bearing solid tumors these existing proteasome inhibitors have demonstrated poor results. Notably, all three FDA-approved proteasome inhibitors rely on the combination a peptide backbone and reactive …

A Program Evaluation Of A Colon Cancer Screening Program Using At-Home Fecal Immunochemical Tests With Certified Patient Navigators, Candace E. H. Brunk

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Colorectal cancer is the second leading cause of cancer-related death in this country, but 33% of these deaths could be prevented by screening. While colonoscopy is an effective screening tool, it is expensive, invasive, and prone to encounter considerable patient resistance. An alternative is to first screen those at-risk using at-home fecal immunochemical test (FIT) kits. This study determined factors associated with the return of these kits distributed by Kentucky CancerLink, a non-profit organization, and its affiliates to participants in a colon cancer prevention program.

Objectives: To identify factors associated with: completing a FIT kit, completing the kit with minimal …

The Role Of Progesterone Receptor Membrane Component 1 In Receptor Trafficking And Disease, Kaia K. Hampton

Theses and Dissertations--Pharmacology and Nutritional Sciences

The progesterone receptor membrane component 1 (PGRMC1) is a multifunctional protein with a heme-binding domain that promotes cellular signaling via receptor trafficking, and is essential for some elements of tumor growth and metastasis. PGRMC1 is upregulated in breast, colon, lung and thyroid tumors. We expanded the analysis of PGRMC1 in the clinical setting, and report the first analysis of PGRMC1 in human oral cavity and ovarian tumors and found PGRMC1 to correlate with lung and ovarian cancer patient survival. Furthermore, we discovered a specific role for PGRMC1 in cancer stem cell viability. PGRMC1 directly associates with the epidermal growth factor …

Surface-Initiated Polymerizations For The Rapid Sorting Of Rare Cancer Cells, Jacob L. Lilly

Theses and Dissertations--Chemical and Materials Engineering

Cancer metastasis directly accounts for an estimated 90% of all cancer related deaths and is correlated with the presence of malignant cells in systemic circulation. This observed relationship has prompted efforts to develop a fluid biopsy, with the goal of detecting these rare cells in patient peripheral blood as surrogate markers for metastatic disease as a partial replacement or supplement to tissue biopsies. Numerous platforms have been designed, yet these have generally failed to support a reliable fluid biopsy due to poor performance parameters such as low throughput, low purity of enriched antigen positive cells, and insufficiently low detection thresholds …

Evaluating Adherence To Colorectal Cancer Screening, Jaime Bradley-Miller

DNP Projects

Purpose: The purpose of this project and literature review was to determine provider documentation practices of colorectal cancer (CRC) screening, identify the percent of clinic patients who need to be screened, and develop a set of recommendations and targeted interventions which will increase CRC screening rates.

Methods: A retrospective chart review including males and females of all ethnicities between the ages of 45 and 80 was performed in one primary care practice. A randomized sample of 360 office visits between February and November of 2015 were selected, of which 281 met the inclusion and exclusion criteria. Patient demographics and characteristics …

Evaluation Of Diet Composition Of Pediatric Cancer Survivors As A Need For Nutrition Counseling, Sean O'Nan

Theses and Dissertations--Nutrition and Food Systems

Prior research has shown that pediatric cancer survivors face a multitude of longterm effects from treatment of their disease. Many of these conditions can be treated or managed through proper nutrition, however patients of the DanceBlue Kentucky Children's Hospital Hematology/Oncology Clinic do not see a registered dietitian. This study looked at food and drink consumption of the past 30 days by the patient using the NHANES Dietary Screener Questionnaire to see if they met nutrition recommendations as outlined by the 2015‐2020 Dietary Guidelines for Americans. Results from the study found that off‐treatment pediatric cancer survivors (n=21) failed to meet …

Investigating Mechanisms Determining Cancer Cell Sensitivity To Carfilzomib And Novel Strategies To Overcome Resistance, Lin Ao

Theses and Dissertations--Pharmacy

Proteasome inhibitors (PIs) are a class of FDA-approved anti-cancer agents which includes the first-generation PI bortezomib (BTZ) and second-generation carfilzomib (CFZ). Drug resistance is a major challenge in PI therapy with no solution currently available. While a few resistance mechanisms had been proposed for BTZ, little was known about CFZ resistance before the start of our studies. In this dissertation work, we investigated multiple mechanisms contributing to CFZ resistance—alterations in the drug transporter activity, metabolic stability, and proteasome activity profiles—and evaluated potential strategies to overcome CFZ resistance.

We observed marked upregulation of the drug efflux transporter P-glycoprotein (P-gp) in our …

The Metabolomic Effects Of Metformin On Colon Cancer, Jennifer W. Harris

Theses and Dissertations--Clinical and Translational Science

Metformin is an oral biguanide that is prescribed to over 120 million people worldwide for the treatment of conditions including type II diabetes mellitus, polycystic ovarian syndrome, and gestational diabetes. This hypoglycemic agent is rapidly emerging as a potential cost-effective anti-oncogenic agent. Over the past decade multiple epidemiologic studies have consistently associated metformin with decreased cancer incidence and cancer-related mortality. More recently numerous preclinical and clinical studies have demonstrated anti-cancer effects of metformin, leading to the proposal of numerous clinical trials to better understand this drug and its mechanism of action.

Previously experts believed metformin primarily targeted AMP-activated protein kinase …

Clinical And Pathologic Significance Of Integrin Α6Β4 Expression In Human Malignancies, Rachel L. Stewart

Theses and Dissertations--Clinical and Translational Science

Integrins are cellular adhesion molecules that bind cells to the extracellular matrix. The integrin α6β4, a receptor for laminins, is predominantly expressed on epithelial cells where it is present at the basal surface adjacent to the basement membrane. This integrin plays a critical role in maintaining normal cellular functions, yet has also been implicated in promoting invasion and metastasis in human malignancies. While overexpression of the integrin α6β4 has been detected in select human cancers, the clinical significance of integrin α6β4 expression in a number of malignancies has not been determined. The purpose of this study was to examine integrin …

Are There Delays In Receipt Of Treatment Among Appalachian Kentucky Women With Breast Cancer, Huong Thi Thanh Luu

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Background: Women living in rural and under-resourced Appalachian Kentucky may experience delays in receiving cancer treatment yet such delays have not been systematically evaluated. In this analysis, we hypothesize that women diagnosed with breast cancer who live in Appalachian Kentucky would be more likely to have a treatment delay compared to those living in other Kentucky regions and adjusting for individual measures of socioeconomic status.

Methods: In this cohort study, women included in the Kentucky Cancer Registry with a diagnosis of an incident, primary breast cancer in the prior 12 months were interviewed by phone (n=1,245; response rate 26.9%). Cox …

Polymer Micelles For Tunable Drug Release And Enhanced Antitumor Efficacy, Andrei G. Ponta

Theses and Dissertations--Pharmacy

Cancer remains a leading cause of death in the United States. The most common treatment options include chemotherapy, but poor solubility, adverse side effects and differential drug sensitivity hamper clinical applications. Current chemotherapy generally aims to deliver drugs at the limit of toxicity, assuming that higher dosage increases efficacy, with little attention paid to potential benefits of tunable release. Growing evidence suggests that releasing drugs at a constant rate will be as effective as a single bolus dose. To test this hypothesis, it is critical to develop drug delivery systems that fine-tune drug release and elucidate the impact of tunable …

Getting To The Other Side: An Exploration Of The Head And Neck Cancer Treatment Experience, Heather M. Wallace

Theses and Dissertations--Gerontology

Diagnosis of head and neck squamous cell carcinoma (HNSCC) presents a multifarious problem. Late stage diagnosis, uncertainty regarding appropriate clinical treatment, as well as the high potential for disfigurement and functional loss resulting in diminished quality of life, contributes to anxiety, stress, fear, and uncertainty throughout the cancer treatment experience. This qualitative study sought to explore the cancer treatment experience of adults with newly diagnosed HNSCC, including laryngeal, esophageal, and oral cancers. Study participants were recruited from the University of Kentucky Ear Nose and Throat Clinic in Lexington KY. Participants agreed to be interviewed after receipt of their cancer diagnosis …

Structural Instability Of Human Ribosomal Rna Gene Clusters, Dawn Michelle Stults

University of Kentucky Doctoral Dissertations

The human ribosomal RNA genes are critically important for cell metabolism and viability. They code for the catalytic RNAs which, encased in a housing of more than 80 ribosomal proteins, link together amino acids by peptide bonds to generate all cellular proteins. Because the RNAs are not repeatedly translated, as is the case with messenger RNAs, multiple copies are required. The genes which code for the human ribosomal RNAs (rRNAs) are arranged as clusters of tandemly repeated sequences. Three of four catalytic RNAs are spliced from a single transcript. The genes are located on the short arms of the five …

Human Ribosomal Rna Gene Clusters Are Recombinational Hotspots In Cancer, Dawn Michelle Stults

University of Kentucky Master's Theses

The gene that produces the precursor RNA transcript to the three largest ribosomal RNA molecules (rDNA) is present in multiple copies and organized into gene clusters. They represent 0.5% of the diploid human genome but are critical for cellular viability. The individual genes possess very high levels of sequence identity and are present in high local concentration, making them ideal substrates for genomic rearrangement driven by dysregulated homologous recombination. Our laboratory has developed a sensitive physical assay capable of detecting recombination-mediated genomic restructuring in the rDNA by monitoring changes in lengths of the individual clusters. In order to determine whether …